Production of virus-like particles (VLPs) typically involves expression and assembly of the VLPs in host cell expression systems. For removing infectious agents from the resulting production cultures, virus filtration is commonly used, though other methods such as UV inactivation or chemical inactivation may also used (either alone or in conjunction with filter-based methods). However, for larger biological components such as VLPs, virus filtration is not available as the VLPs are often too close in size to infectious agents (e.g., viruses) to be capable of being separated from such infectious agents by filtration alone.
In a particular example, following baculovirus expression of VLPs in Sf9 insect cells, the resulting bulk production cultures contain high levels of process contaminants including host cell proteins, nucleic acids and live infectious agents, including baculovirus. While harvest of VLP production culture by low speed centrifugation and filtration generates a clarified sample suitable for downstream purification, these methods are not suitable for removal of host cell protein and live viruses, including baculovirus. Therefore, other methods are needed to inactivate infectious agents and/or clear process contaminants during harvest to facilitate downstream processing when preparing VLPs.